The Ratchet Model of Synovial Flares in Palindromic Rheumatism

Abstract

Synovial flares in palindromic rheumatism (PR) are aperiodic bursts of inflammation in the joints, which usually self-resolve in a timescale hours or days. PR patients are believed to transit to a chronic auto-immune disease called rheumatoid arthritis (RA) in most cases, however, many patients remain palindromic indefinitely. We utilize and adapt a minimal ODE model of rheumatoid arthritis (RA) developed by Baker et al. to study PR in greater detail. We address questions characterizing the incidence, decay and sustenance of synovial flares in palindromic patients. A key question is to describe the nature of the transition from palindromic to full RA. We show that PR flares ordinarily resolve spontaneously, however, there is a secondary equilibrium in the model into which the trajectory can sometimes get trapped. When this "meta-stable locking" occurs, it initiates an adaptation that helps rescue the flare. Furthermore, this adaptation in turn activates a secondary adaptation in response to fluctuations in the healthy steady state. Finally, we show that if metastable locking occurs frequently enough these adaptation sequences turn maladaptive and the system slowly progresses into fully developed RA.